Tributylphosphine → 6-(2,2-difluoroethoxy)-3-(3,4-dimethoxybenzyl)-7-fluoro-1-(tetrahydro-2H-pyran-4-yl)-quinazoline-2,4(1H,3H)-dione

HRID 1022488Notes

Reaction equation

HRID 1022488 reaction equation
[F:1][C:2]([F:5])(O)[CH3:3].C(P(CCCC)CCCC)CCC.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[CH3:33][O:34][C:35]1[CH:36]=[C:37]([CH:59]=[CH:60][C:61]=1[O:62][CH3:63])[CH2:38][N:39]1[C:48](=[O:49])[C:47]2[C:42](=[CH:43][C:44]([F:51])=[C:45]([OH:50])[CH:46]=2)[N:41]([CH:52]2[CH2:57][CH2:56][O:55][CH2:54][CH2:53]2)[C:40]1=[O:58]>C1COCC1>[F:1][CH:2]([F:5])[CH2:3][O:50][C:45]1[CH:46]=[C:47]2[C:42](=[CH:43][C:44]=1[F:51])[N:41]([CH:52]1[CH2:57][CH2:56][O:55][CH2:54][CH2:53]1)[C:40](=[O:58])[N:39]([CH2:38][C:37]1[CH:59]=[CH:60][C:61]([O:62][CH3:63])=[C:35]([O:34][CH3:33])[CH:36]=1)[C:48]2=[O:49]

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 20243757DifluoroethanolHCID 497649193-(3,4-dimethoxybenzyl)-7-fluoro-6-hydroxy-1-(tetrahydro-2H-pyran-4-yl)quinazoline-2,4(1H,3H)-dione

Product 1

HCID 497649206-(2,2-difluoroethoxy)-3-(3,4-dimethoxybenzyl)-7-fluoro-1-(tetrahydro-2H-pyran-4-yl)-quinazoline-2,4(1H,3H)-dioneYield 82.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

0.125 g of difluoroethanol, 0.47 g of tributylphosphine and 0.38 g of DIAD are successively added to a solution of 0.4 g of the compound obtained in Step 4.7 in 15 ml of THF. This mixture is stirred overnight at room temperature. The reaction medium is evaporated under reduced pressure. The residue is chromatographed on silica gel, eluting with a PE/EtOAc mixture from (100/0, v/v) to (30/70) to give 0.38 g of the expected product.

Workup

  1. customThe reaction medium is evaporated under reduced pressure
  2. customThe residue is chromatographed on silica gel
  3. washeluting with a PE/EtOAc mixture from (100/0

Sources & evidence

ORD record
ord-0a265e92edec47c5bf256017413e63b2
Source dataset
uspto-grants-2014_05
Patent number
US08722659B2

Reaction notes

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